WO1997038000A1 - Process for preparing erythromycin a oxime - Google Patents
Process for preparing erythromycin a oxime Download PDFInfo
- Publication number
- WO1997038000A1 WO1997038000A1 PCT/US1997/003177 US9703177W WO9738000A1 WO 1997038000 A1 WO1997038000 A1 WO 1997038000A1 US 9703177 W US9703177 W US 9703177W WO 9738000 A1 WO9738000 A1 WO 9738000A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oxime
- erythromycin
- isopropanol
- added
- acetic acid
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 8
- KYTWXIARANQMCA-PGYIPVOXSA-N (3r,4s,5s,6r,7r,9r,10z,11s,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-10-hydroxyimino-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradec Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N\O)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 KYTWXIARANQMCA-PGYIPVOXSA-N 0.000 title description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 54
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 49
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims abstract description 22
- 229960003276 erythromycin Drugs 0.000 claims abstract description 21
- 229930006677 Erythromycin A Natural products 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000011541 reaction mixture Substances 0.000 claims description 12
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 10
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 8
- 229960002626 clarithromycin Drugs 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
- 230000001035 methylating effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- SVWLIIFHXFGESG-UHFFFAOYSA-N formic acid;methanol Chemical compound OC.OC=O SVWLIIFHXFGESG-UHFFFAOYSA-N 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- KYTWXIARANQMCA-RWJQBGPGSA-N (3r,4s,5s,6r,7r,9r,11s,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-10-hydroxyimino-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2 Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=NO)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 KYTWXIARANQMCA-RWJQBGPGSA-N 0.000 description 1
- CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000003386 deoximation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000011935 selective methylation Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Definitions
- the field of the present invention is erythromycin A 9-oxime production. More particularly the present invention pertains to the production of 9-oxime erythromycin A using isopropanol and acetic acid.
- 6-O-methylerythromycin A (clarithromycin), shown below, is a potent macrolide antibiotic (United States Patent No. 4,331,803).
- 6-O-methylerythromycin A can also be made from 9-oxime erythromycin A derivatives (See, e.g., United States Patent Nos. 5,274,085; 4,680386; 4,668776; 4,670,549, 3,478,014 and 4,672,109 and European Patent Application 0260938 A2).
- the oxime can be made by reacting erythromycin A with either hydroxylamine hydrochloride and a base or free hydroxylamine in methanol and an organic acid (see, e.g., United States Patent Nos. 3,478,014 and 5,274,085).
- the existing methods of making 9-oxime erythromycin A result in the production of degradation impurities.
- the present invention provides a new and improved process of preparing 9-oxime erythromycin A. That process used a mild acid catalyst in combination with a mildly polar solvent.
- erythromycin A is reacted with hydroxylamine in the presence of acetic acid and isopropanol.
- aqueous hydroxylamine is added to a solution of erythromycin A in isopropanol to form a reaction mixture and then acetic acid is added to the reaction mixture.
- aqueous hydroxylamine is mixed with acetic acid to form a mixture and the mixture is then added to a solution of erythromycin A in isopropanol.
- isopropyl alcohol provides a homogenous reaction mixture.
- acetic acid gives less degradation impurities.
- Advantages of the process of the present invention include a significant improvement in yield, ease of liquid reagent handling, the ready availability of the starting materials, reagents and solvent, and the direct recycling of the process solvents into the later stage of antibiotic (clarithromycin) synthesis.
- the preparation of 9-oxime erythromycin A begins with erythromycin A which is dissolved in isopropanol. An aqueous solution of hydroxylamine is added to the erythromycin /isopropanol to form a reaction mixture. Acetic acid is then added to the reaction mixture.
- the reaction mixture is maintained at a suitable temperature for a period of time sufficient for 9-oxime formation. Temperature can range from about 35°C to about 65°C. Preferably, the temperature is from about 45°C to about 55°C and, more preferably about 50°C.
- reaction mixture is cooled to about room temperature. Isopropyl acetate is added to the cooled reaction mixture and the reaction mixture stirred. During stirring, the reaction mixture is titrated to a pH value of > 11.0 with sodium hydroxide. The organic layer is washed with a dilute caustic and concentrated to dryness to give 9-oxime erythromycin A.
- the acetic acid can be pre-mixed with the hydroxylamine free base prior to mixing it with erythromycin A. This allows for reduction of the exotherm upon erythromycin A addition.
- 9-Oxime erythromycin A prepared in accordance with a process of the present invention can then be used to prepare 6-O-methylerythromycin A in accordance with standard procedures well known in the art.
- Those subsequent steps include the steps of protecting the 9-oxime group as well as the 2'-hydroxy group (with or without optional protection of the 3'-dimethylamine and 4"-hydroxy group), selective methylation of the 6- hydroxy group, deprotection of the protected groups and deoximation.
- Those steps can be carried out by a variety of means known in the art (See, e.g., U.S. Patent Nos. 5,274,085; 4,680,386; 4,668,776; 4,670,549 and 4,672,109 and European Patent Application 0260938 A2).
- 9-Oxime erythromycin A was prepared in accordance with the procedures of Example 1 except that various combinations of acids and alcohols were used in addition to acetic acid and isopropanol. Those other combinations included methanol (MeOH) with formic acid (HCOOH), isopropanol (IPA) with HCOOH, MeOH with acetic acid (HOAc), IPA with HOAc and ethanol (EtOH) with HOAc. The results of those studies are summarized below in Table 1.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT97907949T ATE232210T1 (de) | 1996-04-10 | 1997-02-27 | Verfahren zur herstellung von erythromicin a-oxim |
| DK97907949T DK0970099T3 (da) | 1996-04-10 | 1997-02-27 | Fremgangsmåde til fremstilling af erythromycin A-oxim |
| JP53618597A JP4004068B2 (ja) | 1996-04-10 | 1997-02-27 | エリスロマイシンａオキシムの製造方法 |
| EP97907949A EP0970099B1 (de) | 1996-04-10 | 1997-02-27 | Verfahren zur herstellung von erythromicin a-oxim |
| DE69718942T DE69718942T2 (de) | 1996-04-10 | 1997-02-27 | Verfahren zur herstellung von erythromicin a-oxim |
| CA002250941A CA2250941C (en) | 1996-04-10 | 1997-02-27 | Process for preparing erythromycin a oxime |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/630,306 US5808017A (en) | 1996-04-10 | 1996-04-10 | Process for preparing erythromycin A oxime |
| US08/630,306 | 1996-04-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997038000A1 true WO1997038000A1 (en) | 1997-10-16 |
Family
ID=24526649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/003177 WO1997038000A1 (en) | 1996-04-10 | 1997-02-27 | Process for preparing erythromycin a oxime |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5808017A (de) |
| EP (1) | EP0970099B1 (de) |
| JP (1) | JP4004068B2 (de) |
| AT (1) | ATE232210T1 (de) |
| DE (1) | DE69718942T2 (de) |
| DK (1) | DK0970099T3 (de) |
| ES (1) | ES2191821T3 (de) |
| WO (1) | WO1997038000A1 (de) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999002541A2 (en) * | 1997-07-08 | 1999-01-21 | Biochemie S.A. | Erythromycin a oxime solvates |
| EP0984020A2 (de) * | 1998-08-21 | 2000-03-08 | Apotex Inc. | Azithromycinmonohydrat-Isopropanol Clathrate und Methoden zu deren Herstellung |
| WO2003040162A1 (de) * | 2001-11-07 | 2003-05-15 | Aventis Pharma Deutschland Gmbh | Verfahren zur herstellung von desclarithromycin, sowie zwischenprodukte |
| CN103897002A (zh) * | 2012-12-31 | 2014-07-02 | 菏泽市方明制药有限公司 | 一种粗品硫氰酸红霉素制备红霉素a9-肟的方法 |
| CN103923142A (zh) * | 2014-04-30 | 2014-07-16 | 浙江震元制药有限公司 | 一种罗红霉素中间体的制备方法 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN190782B (de) * | 1998-09-30 | 2003-08-23 | Max India Ltd | |
| US6437106B1 (en) | 1999-06-24 | 2002-08-20 | Abbott Laboratories | Process for preparing 6-o-substituted erythromycin derivatives |
| EP1254146B1 (de) | 1999-12-16 | 2005-08-24 | Teva Pharmaceutical Industries Ltd. | Verfahren zur herstllung von clarithromycin polymorphen und polymorph iv |
| US6590084B2 (en) | 1999-12-20 | 2003-07-08 | Merial | Process for preparing and isolating 9-deoxo-9 (Z)-hydroxyiminoerythromycin A |
| FR2802534B1 (fr) * | 1999-12-20 | 2002-02-01 | Merial Sas | Procede pour preparer et isoler la 9-deoxo-9 (z)- hydroxyiminoerythromycine a |
| PL356645A1 (en) | 2000-01-11 | 2004-06-28 | Teva Pharmaceutical Industries Ltd. | Processes for preparing clarithromycin polymorphs |
| US6544555B2 (en) | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
| EP1313486A1 (de) * | 2000-02-29 | 2003-05-28 | Teva Pharmaceutical Industries Ltd. | Verfahren zur herstellung des clarithromycins und eines clarithromycin-zwischenprodukt; clarithromycin wesentlich frei von oxime; und pharmazeutische zusammensetzung die sie enthalten |
| DE60138876D1 (de) * | 2000-03-28 | 2009-07-16 | Sandoz Ag | Geschmackmaskierte granulierte teilchen |
| DE60114028T2 (de) * | 2000-08-23 | 2006-07-13 | Wockhardt Ltd. | Verfahren zur herstellung von wasserfreiem azithromycin |
| US20020068078A1 (en) | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
| EP1648418A4 (de) | 2003-07-21 | 2011-11-16 | Middlebrook Pharmaceuticals Inc | Antibiotisches produkt, seine verwendung und formulierung |
| CA2533292C (en) | 2003-07-21 | 2013-12-31 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
| WO2005009365A2 (en) | 2003-07-21 | 2005-02-03 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
| US8758820B2 (en) | 2003-08-11 | 2014-06-24 | Shionogi Inc. | Robust pellet |
| CA2535398C (en) | 2003-08-12 | 2013-11-12 | Advancis Pharmaceuticals Corporation | Antibiotic product, use and formulation thereof |
| CA2535780A1 (en) * | 2003-08-29 | 2005-03-17 | Advancis Pharmaceuticals Corporation | Antibiotic product, use and formulation thereof |
| AU2004273830B2 (en) | 2003-09-15 | 2011-03-24 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
| EP1771158A4 (de) | 2004-07-02 | 2008-03-12 | Advancis Pharmaceutical Corp | Tablette für pulsierte abgabe |
| US8357394B2 (en) | 2005-12-08 | 2013-01-22 | Shionogi Inc. | Compositions and methods for improved efficacy of penicillin-type antibiotics |
| US8778924B2 (en) | 2006-12-04 | 2014-07-15 | Shionogi Inc. | Modified release amoxicillin products |
| US7595300B2 (en) | 2005-12-13 | 2009-09-29 | Kosan Biosciences Incorporated | 7-quinolyl ketolide antibacterial agents |
| US8299052B2 (en) | 2006-05-05 | 2012-10-30 | Shionogi Inc. | Pharmaceutical compositions and methods for improved bacterial eradication |
| US20090054634A1 (en) * | 2007-08-09 | 2009-02-26 | Vinod Kumar Kansal | Process for the preparation of clarithromycin |
| CN101362783B (zh) * | 2008-10-06 | 2011-12-07 | 浙江国邦药业有限公司 | 一种红霉素a(e)肟的制备方法 |
| CN102911225A (zh) * | 2011-08-04 | 2013-02-06 | 山东方明药业集团股份有限公司 | 红霉素a肟的清洁化合成方法及其特别组合的反应设备 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3478014A (en) * | 1967-08-16 | 1969-11-11 | Pliva Pharm & Chem Works | Erytromycin oxime and 9-amino-3-o-clandinosyl - 5 - o - desosaminyl - 6,11,12 - trihydroxy - 2,4,6,8,10,12 - hexamethyl - pentadecane-olide |
| US4150220A (en) * | 1977-02-04 | 1979-04-17 | Pfizer Inc. | Semi-synthetic 4"-erythromycin A derivatives |
| US4526889A (en) * | 1982-11-15 | 1985-07-02 | Pfizer Inc. | Epimeric azahomoerythromycin A derivative, intermediates and method of use |
| US5274085A (en) * | 1988-05-19 | 1993-12-28 | Taisho Pharmaceutical Co., Ltd. | Process for preparing erythromycin A oxime or a salt thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60214796A (ja) * | 1984-04-06 | 1985-10-28 | Taisho Pharmaceut Co Ltd | ６−０−メチルエリスロマイシン類の製法 |
-
1996
- 1996-04-10 US US08/630,306 patent/US5808017A/en not_active Expired - Lifetime
-
1997
- 1997-02-27 EP EP97907949A patent/EP0970099B1/de not_active Expired - Lifetime
- 1997-02-27 AT AT97907949T patent/ATE232210T1/de not_active IP Right Cessation
- 1997-02-27 DK DK97907949T patent/DK0970099T3/da active
- 1997-02-27 ES ES97907949T patent/ES2191821T3/es not_active Expired - Lifetime
- 1997-02-27 DE DE69718942T patent/DE69718942T2/de not_active Expired - Fee Related
- 1997-02-27 WO PCT/US1997/003177 patent/WO1997038000A1/en active IP Right Grant
- 1997-02-27 JP JP53618597A patent/JP4004068B2/ja not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3478014A (en) * | 1967-08-16 | 1969-11-11 | Pliva Pharm & Chem Works | Erytromycin oxime and 9-amino-3-o-clandinosyl - 5 - o - desosaminyl - 6,11,12 - trihydroxy - 2,4,6,8,10,12 - hexamethyl - pentadecane-olide |
| US4150220A (en) * | 1977-02-04 | 1979-04-17 | Pfizer Inc. | Semi-synthetic 4"-erythromycin A derivatives |
| US4526889A (en) * | 1982-11-15 | 1985-07-02 | Pfizer Inc. | Epimeric azahomoerythromycin A derivative, intermediates and method of use |
| US5274085A (en) * | 1988-05-19 | 1993-12-28 | Taisho Pharmaceutical Co., Ltd. | Process for preparing erythromycin A oxime or a salt thereof |
Non-Patent Citations (1)
| Title |
|---|
| E.H. MASSEY ET. AL.: "Erythromycylamine", TETRAHEDR. LETT., vol. 2, 1970, pages 157 - 60, XP000654484 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999002541A2 (en) * | 1997-07-08 | 1999-01-21 | Biochemie S.A. | Erythromycin a oxime solvates |
| WO1999002541A3 (en) * | 1997-07-08 | 1999-04-01 | Biochemie Sa | Erythromycin a oxime solvates |
| US6504017B1 (en) * | 1997-07-08 | 2003-01-07 | Biochemie S.A. | Erthromycin a oxime solvates |
| EP0984020A2 (de) * | 1998-08-21 | 2000-03-08 | Apotex Inc. | Azithromycinmonohydrat-Isopropanol Clathrate und Methoden zu deren Herstellung |
| EP0984020A3 (de) * | 1998-08-21 | 2000-10-04 | Apotex Inc. | Azithromycinmonohydrat-Isopropanol Clathrate und Methoden zu deren Herstellung |
| WO2003040162A1 (de) * | 2001-11-07 | 2003-05-15 | Aventis Pharma Deutschland Gmbh | Verfahren zur herstellung von desclarithromycin, sowie zwischenprodukte |
| CN103897002A (zh) * | 2012-12-31 | 2014-07-02 | 菏泽市方明制药有限公司 | 一种粗品硫氰酸红霉素制备红霉素a9-肟的方法 |
| CN103923142A (zh) * | 2014-04-30 | 2014-07-16 | 浙江震元制药有限公司 | 一种罗红霉素中间体的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US5808017A (en) | 1998-09-15 |
| EP0970099A1 (de) | 2000-01-12 |
| ES2191821T3 (es) | 2003-09-16 |
| DK0970099T3 (da) | 2003-05-26 |
| DE69718942D1 (de) | 2003-03-13 |
| JP4004068B2 (ja) | 2007-11-07 |
| ATE232210T1 (de) | 2003-02-15 |
| DE69718942T2 (de) | 2003-12-11 |
| EP0970099B1 (de) | 2003-02-05 |
| JP2000508311A (ja) | 2000-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0970099B1 (de) | Verfahren zur herstellung von erythromicin a-oxim | |
| US6013778A (en) | Process for the preparation of azithromycin | |
| RU2230748C2 (ru) | Способ получения кларитромицина в виде кристаллов формы ii | |
| EP0891370B1 (de) | 2'-geschützter 3'-dimethylamin, 9-etheroxim erythromycin a derivate | |
| JP2657132B2 (ja) | アジスロマイシンａのｏ−メチル誘導体、その製造法、その製造中間体及びそれを含有する抗菌剤組成物 | |
| EP0915899B1 (de) | Herstellung von kristallinen form ii von clarithromycin | |
| EP0240264B1 (de) | Verfahren zur Herstellung von Makrolidderivaten | |
| CA2327775C (en) | 15-membered lactams ketolides with antibacterial activity | |
| IL135517A (en) | Synthesis of 6-0-methyl erythromycin A and some new derivatives of 9- (di-converted to benzoyl) oxides derived therefrom | |
| JP2001520234A (ja) | ９ａ−アザリド類から誘導される新規３，６−ヘミケタール類 | |
| CA2250941C (en) | Process for preparing erythromycin a oxime | |
| JP2002542254A (ja) | 新規な８ａ−及び９ａ−１５員ラクタム類 | |
| CN106977569A (zh) | 6‑亚甲基‑17α‑羟基孕酮醋酸酯的制备方法 | |
| JP2001506281A (ja) | エリスロマイシンａオキシム溶媒和物 | |
| US6613889B2 (en) | Method for preparing salts of polyene macrolide esters | |
| KR100347094B1 (ko) | 6-오-메틸에리트로마이신에이제2형의제조방법 | |
| EP1633764B1 (de) | Regioselektives verfahren zur herstellung von o-alkyl makrolid und azalid derivaten | |
| CN1267443C (zh) | 大环内酯类抗生素中间体及其制备 | |
| PL191831B1 (pl) | Sposób otrzymywania 6-O-alkiloerytromycyny A oraz półprodukty zastosowane w tym sposobie | |
| CA2038629C (en) | Oleandomycin oximes, preparation and use thereof | |
| CN115010767A (zh) | 一种乙酰氨基阿维菌素及其制备方法 | |
| WO2005021567A1 (en) | O-alkyl macrolide and azalide derivatives and regioselective process for their preparation | |
| KR20000037127A (ko) | 에리스로마이신 ａ 6-메틸 유도체의 제조방법 | |
| EP0490311A1 (de) | Derivate von 10,11,12,13-tetra-hydrodesmycosin, Verfahren zu ihrer Herstellung, und ihre Verwendung zur Herstellung von Arzneimitteln | |
| EP0972778A1 (de) | Erythromycin A Derivate und Verfahren zu deren Herstellung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA JP MX |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 1997907949 Country of ref document: EP |
|
| ENP | Entry into the national phase |
Ref document number: 2250941 Country of ref document: CA Ref country code: CA Ref document number: 2250941 Kind code of ref document: A Format of ref document f/p: F |
|
| WWE | Wipo information: entry into national phase |
Ref document number: PA/a/1998/008370 Country of ref document: MX |
|
| WWP | Wipo information: published in national office |
Ref document number: 1997907949 Country of ref document: EP |
|
| WWG | Wipo information: grant in national office |
Ref document number: 1997907949 Country of ref document: EP |